Over the last several years it has become apparent that the neurotransmitter serotonin (5-hydroxytryptamine--5-HT) is associated directly or indirectly with a number of physiological phenomena, including appetite, memory, thermoregulation, sleep, sexual behavior, anxiety, depression, and hallucogenic behavior [Glennon, R. A. , J. Med. Chem. 30, 1 (1987) ].
It has been recognized that there are multiple types of 5-HT receptors. These receptors have been classified as 5-HT.sub.1, 5-HT.sub.2, and 5-HT.sub.3 receptors, with the former being further divided into the sub-classes 5-HT.sub.1A, 5-HT.sub.1B, 5-HT.sub.1C, and 5-HT.sub.1D.
Selected 2-amino-1,2,3,4-tetrahydronaphthalenes (2-aminotetralins) and 3-aminochromanes have been shown to exhibit binding affinity at the 5-HT.sub.1A receptor.
Co-pending application Ser. No. 315,750 filed Feb. 27, 1989, abandoned and refiled as Ser. No. 683,637, Apr. 11, 1991 and U.S. Pat. No. 5,389,687 describes certain 2-aminotetralins substituted in the 8-position by formyl, cyano, halo, hydroxymethyl, carboxamido, carboxyl, or alkoxycarbonyl. The compounds are described as exhibiting high binding affinity at the 5-HT.sub.1A receptor. In addition, co-pending application Ser. No. 315,752 filed Feb. 27, 1989, now abandoned, describes other 2-aminotetralins substituted in the 8-position and 3-aminochromanes substituted in the 5-position by sulfides, sulfoxides, and sulfones. These compounds, as well, are described as having binding affinity at the 5-HT.sub.1A receptor. A further class of 2-aminotetralins substituted in the 8-position and 3-aminochromanes substituted in 5-position by an acyl group and having 5-HT.sub.1A agonist activity is described in co-pending application Ser. No. 567,985 filed Aug. 15, 1990 abandoned and refiled as Ser. No. 48,553, Apr. 16, 1993, now U.S. Pat. No. 5,286,753. Another class of 2-aminotetralins are described in European Patent Application No. 343,830, published Nov. 29, 1989. These compounds have a piperazinyl or homopiperazinyl moiety in the 2-position and, distinct from the foregoing tetralins, exhibit serotonin re-uptake inhibition as opposed to serotonin receptor binding affinity. We have now discovered a further class of compounds which, by reason of their 5-HT.sub.1A activity, are useful in the treatment, for example, of sexual dysfunction, anxiety, depression, and eating disorders, such as anorexia.